Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody.
Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment.
Stewart
J S
JS
Imperial Cancer Research Fund, Hammersmith Hospital, London, United Kingdom.
Sivolapenko
G B
GB
Hird
V
V
Davies
K A
KA
Walport
M
M
Ritter
M A
MA
Epenetos
A A
AA
D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001853:Bone Marrow / Q000528:radiation effects; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007167:Immunotherapy; D007457:Iodine Radioisotopes / Q000009:adverse effects; D008099:Liver / Q000528:radiation effects; D008562:Membrane Glycoproteins / Q000276:immunology; D018396:Mucin-1; D010051:Ovarian Neoplasms / Q000628:therapy; D011879:Radiotherapy Dosage
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D018396:Mucin-1